The heritability of metabolite concentrations in stored human red blood cells
van 't Erve, T.J., Wagner, B.A., Martin, S.M. et al.
The degeneration of red blood cells (RBCs) during storage is a major issue in transfusion medicine. Family studies in the 1960s established the heritability of the RBC storage lesion based on post-storage ATP concentrations. However, this critical discovery has not been further explored. In a classic twin study we confirmed the heritability of post-storage ATP concentrations and established the heritability of many other RBC metabolites.
STUDY DESIGN AND METHODS
ATP concentrations and metabolomic profiles were analyzed in RBC samples from 18 twin pairs. On samples stored 28 days the heritability of post-storage ATP concentrations were 64% and 53% in CP2D and AS-3 stored RBCs, respectively.
Metabolomic analyses identified 87 metabolites with an estimated heritability of 20% or greater. Thirty-six metabolites were significantly correlated with ATP concentrations (p ≤ 0.05) and 16 correlated with borderline significance (0.05 ≤ p ≤ 0.10). Of the 52 metabolites that correlated significantly with ATP, 24 demonstrated ≥20% heritability. Pathways represented by heritable metabolites included glycolysis, membrane remodeling, redox homeostasis and synthetic and degradation pathways.
We conclude that many RBC metabolite concentrations are genetically influenced during storage. Future studies of key metabolic pathways and genetic modifiers of RBC storage could lead to major advances in RBC storage and transfusion therapy.
van 't Erve, T.J., Wagner, B.A., Martin, S.M. et al. "The heritability of metabolite concentrations in stored human red blood cells" Transfusion (2014): 2,055–63